2 3-dihydro-2-(5-nitro-2-thienyl)quinazolin-4(1h)ones

ABSTRACT

A SERIES OF 2,3-DIHYDRO-2-(5-NITRO-2-THIENYL)QUINAZOLIN4(1H)ONES OF THE FORMULA:   2-(2-(O2N-)THIEN-5-YL),4-(O=),6-R-1,2,3,4-TETRAHYDRO   QUINAZOLINE   WHEREIN R IS HYDROGEN, CHLORO OR NITRO ARE ESPECIALLY INIMICAL TO HEMOPHILUS VAGINALIS.

United States Patent "ice Patented Feb. 29, 1972 0 3,646,034 H N g R 2,3-DIHYDRO-2-(5-NITRO-2-THIENYL) 2 H01 QUINAZOLIN-4(1H)ONES I m Robert J. Alaimo, Norwich, N.Y., assignor to The 5 N CHO H2N Norwich Pharmacal Company No Drawing. Filed May 18, 1970, Ser. No. 38,553 Int. Cl. C07d 51/48 ii Us. or. 260-251 QA 4 Claims l HN C R 02N g S ABSTRACT OF THE DISCLOSURE A series of 2,3-dihydro-2-(5-nitro-2-thienyl)quinazolinwherein R is as above defined and is i yl, efhyl 4(1H)Ones of the formula; lsopropyl. Brlefly this method conslsts 1n brlnglng to gether the aldehyde and the appropriate anthranilamide in the presence of a solvent such as ethanol under acid conditions preferably followed by heating until the reaction is completed and then filtering.

In order that this invention may be readily understood '5 by and available to those skilled in the art the follow- W R ing examples are set forth:

C l 4] EXAMPLE I OzN-ks 2,3-dihydro-6-m'tro-2- 5-nitro-2-thienyl) quinazolin-4 lI-I) one A mixture of 2-amino-5-nitrobenzamide (2.3 g., .012

mole) in 32 ml. of ethanol was treated with 5-nitro-2- thiophenecarboxaldehyde in 6.4 ml. of ethanol and 1 ml.

. of concentrated hydrochloric acid. The reaction mixture d 135 g f zij t 2 3 2;? or mm) are peel y was refluxed with stirring for 2 hours. The resulting solummnca O em p g tion was cooled in the refrigerator overnight and filtered to yield a yellow brown solid (2 g., 52%). Recrystalli- The invention relates to chemical compounds. More 33 2 ethanol 2 gave 11 P. of

particularly it is concerned with 2,3-dihydro-2-(5-n1tro-2- l 35 na yszs.Calcd. for C H N O S (percent). C, 45.00,

thlenynqumazolm 4(1H)0nes of the formula H, 2.52; N, 17.50. Found (percent): 0, 44.97; H, 2.52;

EXAMPLE II 6-chloro-2,3-dihydro-2-(5-nitro-2-thienyl) (I) quinazolin-4( 1H) one A A warm solution of 171 g. (1.0 mole) of 2-arnino-5- \C R chlorobenzamide in 2500 ml. of ethanol was treated with 0 i II a warm solution of 157 g. (1.0 mole) of 5-nitro-2-thio- 2 phenecarboxaldehyde in 500 ml. of ethanol, conc. HCl

H g (30 ml.) was added and the mixture was heated on a steam bath for 1 hour. The resulting solution was cooled in the refrigerator overnight and the product was collected by filtration as a brown solid in a yield of 208 g.

(67%). Recrystallization from ethanol (Darco) gave yellow needles melting at 196198 C. wherein R 1s h dro en, chloro or nitro.

The memb rs o t this series of compounds are disf for 8 3 3 C, tinguished in their ability to inhibit H em'ophilus vaginalis, Found (Perceno- C, 46-42, the organism frequently implicated in bacterial vaginitis.

Under the commonly employed serial dilution technique EXAMPLE HI members of this series are capable of inhibiting the 2,3-dihydro-2-(S-nitro-Z-thienyl)quinazolin-4(1H)one growth of that Organism in y Small amounts ranging A solution of 5 nitro 2 thiophenecarboxaldehyde from 0. -5 micrograms p mrllilitery are thus (157.0 g., 1.0 mole) in ethanol 1000 ml.) was warmed adapted for topical applicati n n r o s f m for 60 on a steam bath and treated with 20 ml. of conc. H'Cl. Vaginal administration They can be Comblned as the To it was added with rapid stirring a warm solution of tive ingredient in a suppository or a cream suitable f anthranilamide (136.0 g., 1.0 mole) in ethanol (500 m1.). intravaginal use. In such form, when introduced into the The reaction mixture was heated on a t a b th and rat vagina, persistent antibacterial effect is observed for stirred for 1 hour, then chilled in ice and filtered. The

considerable time period. Such residual antibacterial effeet is extremely desirable in the eradication of bacterial (227 g., 82.5%). Recrystallization from ethanol (EDarco) pathogens associated with bacterial vaginitis. yielded yellow needles which melted at 219-221".

The members of this series of compounds are readily Analysis.Cailcd. for C H N O S (percent): C, 52.35;

prepared. The method currently employed can be repre- H, 3.29; N, 15.26. Found (percent): C, 52.60; H, 3.55; sented by this scheme: N, 15.10.

product was washed with aqueous ethanol and air dried wherein R is hydrogen, chloro or nitro.

References Cited UNITED STATES PATENTS 3,162,636 12/ 1964 Gurien et a1. 260-251 5 3,455,920 7/1969 Yale 260-251 ALEX MAZEL, Primary Examiner R. V. RUSH, Assistant Examiner US. Cl. X.R. 424 2s1 2. The compound of claim 1 wherein -R is hydrogen. 3. The compound of claim 1 wherein R is chloro.

4. The compound of claim 1 wherein R is nitro. 

